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Abstract Objective Comorbidity of epilepsy and autism in tuberous sclerosis complex 2 (TSC2) is very frequent, but the link between these conditions is still poorly understood. To study neurological problems related to autism, the scientific community has been using an animal model of TSC2, Tsc2+/− mice. However, it is still unknown whether this model has the propensity to exhibit increased seizure susceptibility. Further, the importance of sex and/or the circadian cycle in this biological process has never been addressed. This research aimed to determine whether male and female Tsc2+/− mice have altered seizure susceptibility at light and dark phases. Methods We assessed seizure susceptibility and progression in a Tsc2+/− mouse model using the chemical convulsant kainic acid (KA), a potent agonist of the AMPA/kainate class of glutamate receptors. Both male and female animals at adult age were evaluated during non‐active and active periods. Seizure severity was determined by integrating individual scores per mouse according to a modified Racine scale. Locomotor behavior was monitored during control and after KA administration. Results We found increased seizure susceptibility in Tsc2+/− mice with a significant influence of sex and circadian cycle on seizure onset, progression, and behavioral outcomes. While, compared to controls, Tsc2+/− males overall exhibited higher susceptibility independently of circadian cycle, Tsc2+/− females were more susceptible during the dark and post‐ovulatory phase. Interestingly, sexual dimorphisms related to KA susceptibility were always reported during light phase independently of the genetic background, with females being the most vulnerable. Significance The enhanced susceptibility in the Tsc2 mouse model suggests that other neurological alterations, beside brain lesions, may be involved in seizure occurrence for TSC. Importantly, our work highlighted the importance of considering biological sex and circadian cycle for further studies of TSC‐related epilepsy research. Plain Language Summary Tuberous sclerosis complex (TSC) is a rare genetic disorder. It causes brain lesions and is linked to epilepsy, intellectual disability, and autism. We wanted to investigate epilepsy in this model. We found that these mice have more induced seizures than control animals. Our results show that these mice can be used in future epilepsy research for this disorder. We also found that sex and time of day can influence the results. This must be considered in this type of research.

Introduction. Patients with a deep bite and dental restorations are at increased risk of unfixing of fixed appliances and other complications due to occlusal defects. The problem of the volume of dental interventions and rational choice of the type, as well as the elimination of complications after their implementation, is relevant and unsolved, especially in patients with disorders of the dental and jaw apparatus, combined with the dentoalveolar form of a deep bite. The aim of the research was to improve the quality of orthodontic treatment of patients with a deep bite, existing reconstructive restorations and occlusal disorders by developing a scientifically based clinical algorithm for fixation of fixed orthodontic equipment. Materials and methods. The main group – 29 patients who were treated according to the scheme of fixation of non-removable equipment developed by us and the use of myorelaxation methods, and the research group – 22 people who were treated with generally accepted method. Methods: questionnaires, clinical and radiological, instrumental and statistical. The results of our experimental study of patients illustrated that the scheme of the proposed algorithm for fixing fixed appliances in the future will have the opportunity to increase the efficiency of providing dental care and will be implemented in the treatment process in patients with a deep bite, because they are in the group of increased risk of unpredicted debonding of fixed orthodontic appliances. Conclusions. The results of our experimental study of patients illustrated that the scheme of the proposed algorithm for fixing fixed appliances in the future will have the opportunity to increase the efficiency of dental care and will be implemented in the treatment process in patients with a deep bite, because they are in the group of increased risk of unpredicted debonding of fixed orthodontic appliances.

Abstract Superstitious beliefs threaten wildlife species, yet they have received limited attention in the scientific literature. Through a mixed‐method approach, including 259 face‐to‐face interviews, we explored the factors influencing superstitions about giant anteaters in the Brazilian Pantanal and their implications for both people and the species. Our results indicated that bad omen superstitions about giant anteaters could be explained by the psychological discomfort felt from the species' peculiarities, social influence, misconceptions about their biology and behaviour, and the frequency of the species' sightings. Age, gender and schooling did not influence superstitious adherence. Interviewees holding superstitious beliefs of bad luck reported worry, distress and anxiety in trigger situations. Most engage in superstitious behaviours to ward off bad luck. While some acts were harmless, others threatened people and giant anteaters. By explaining misconceptions and demystifying unique species characteristics that evoke psychological discomfort, conservationists might foster better coexistence between people and species historically associated with misfortune. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Animal biotechnologies have the potential to improve the sustainability and security of our global food systems. Government regulatory authorities are responsible for ensuring the safety of food their citizens consume, whether it is produced via conventional breeding methods or biotechnologies. While some countries have implemented animal biotechnology oversight policies, many countries have yet to develop theirs. Historically, regulatory approvals were required before products of biotechnology could enter the marketplace, and the high cost of the approval process limited the number and types of animal and plant products that sought approval. Only one biotech animal in the world that was developed for food production has reached the market under a GMO or rDNA approval process. The advent of genome editing techniques has revolutionized the scientific approach to introducing changes into DNA sequences and how biotechnology can be used to enhance agricultural breeding. Regulatory dialogs about biotechnology also have changed as a result of these new technologies. Regulatory agencies have begun to respond to these scientific advances, and a growing number of countries are looking to modernize regulatory approaches for these products, based on risk (or lack thereof) and similarity to organisms that could be produced via conventional breeding methods. Advances in animal biotechnology, especially genome editing, can accelerate the incorporation of valued phenotypes in animals, including enhanced yield, disease resistance, resilience to changing climate, and improved animal welfare, as well as food qualities valued by consumers. For animals with these biotechnology-introduced traits to enter agricultural production and reach consumers, clear risk-proportionate regulatory approaches must be in place, and to facilitate international trade of animal products, regulatory processes need to be aligned and compatible. Effective scientific public communication is crucial to build public trust in precision animal biotechnology and risk-proportionate regulatory approaches. An international workshop on regulatory approaches for animal biotechnology was convened in 2022 with 27 countries represented. We synthesize here technical progress, development of regulatory policy, and strategies for engagement with diverse publics on animal biotechnology reported in the workshop. Our goal is to encourage development and implementation of risk-proportionate regulatory approaches and policies in a global context.

ABSTRACT Invasive species affect ecosystems all over the world. Their impacts intensify when there are beneficial effects among different invasive species, an invasional meltdown. The Argentine black and white tegu lizard, Salvator merianae (Squamata: Teiidae), and the plant Eugenia uniflora (Myrtaceae) are native to mainland South America but behave as invasive species in other parts of the world. We tested the effectiveness of S. merianae as a seed disperser of E. uniflora. Tegu feces containing seeds of E. uniflora were collected to compare the seed germination of gut-passed seeds, manually de-pulped seeds, and seeds of whole fruits. Survival analysis indicated that Tegu lizards behave as seed dispersers of E. uniflora, and there was a tendency for gut-passed seeds to germinate faster than non-gut-passed seeds. Tegu lizards may carry seeds in their guts for considerable distances, facilitating the spread of E. uniflora where both species co-occur as native and invasive (e.g., southern USA). The results indicate a mutualistic interaction between the Tegu lizard and E. uniflora in their native range, which should be considered by initiatives to monitor and control the invasion of the lizard and the plant.

Habitat fragmentation can negatively impact wildlife populations by simplification of ecological interactions, but little is known about how these impacts extend to host-associated symbiotic communities. The symbiotic communities of amphibians play important roles in anti-pathogen defences, particularly against the amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd). In this study, we analyse the role of macroparasitic helminth communities in concert with microbial communities in defending the host against Bd infection within the context of forest fragmentation. We found that skin microbial and helminth communities are disrupted at fragmented habitats, while gut microbiomes appear more resilient to environmental change. We also detected potential protective roles of helminth diversity and anti-pathogen microbial function in limiting Bd infection. Microbial network analysis revealed strong patterns of structure in both skin and gut communities, with helminths playing central roles in these networks. We reveal consistent roles of microbial and helminth diversity in driving host–pathogen interactions and the potential implications of fragmentation on host fitness.

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Postoperative urinary retention (POUR) is a well-known complication after gynecologic surgery. Our objective was to investigate whether the choice of pharmacologic agent for reversing neuromuscular blockade at the end of a hysterectomy is a risk factor for POUR. Among adult patients undergoing hysterectomy with general anesthesia from 2012 to 2017, those who received aminosteroid nondepolarizing neuromuscular agents followed by pharmacologic reversal were identified, and electronic health records were reviewed. The cohort was dichotomized into two groups by reversal agent: 1) sugammadex and 2) neostigmine with glycopyrrolate. The primary outcome, POUR, was defined as unplanned postoperative bladder recatheterization. A propensity-adjusted analysis was performed to investigate the association between POUR and reversal agent by using inverse probability of treatment weighting to adjust for potential confounders. We identified 1,974 patients, of whom 1,586 (80.3%) received neostigmine-glycopyrrolate and 388 (19.7%) received sugammadex for reversal of neuromuscular blockade. The frequency of POUR was 24.8% (393/1,586) after reversal with neostigmine-glycopyrrolate and 18.3% (71/388) with sugammadex. Results from the propensity-adjusted analysis showed that sugammadex was associated with a lower POUR risk than neostigmine-glycopyrrolate (odds ratio 0.53, 95% confidence interval [CI] 0.37 - 0.76, P < 0.001). A post hoc analysis of sugammadex recipients who received glycopyrrolate for another indication showed a higher POUR risk than among those who did not receive glycopyrrolate (odds ratio 1.86, 95% CI 1.07 - 3.22, P = 0.03). Use of sugammadex to reverse aminosteroid neuromuscular blocking agents is associated with decreased risk of POUR after hysterectomy. A potential mechanism is the omission of glycopyrrolate, which is coadministered with neostigmine to mitigate unwanted cholinergic effects.

Abstract Background Supplemental oxygen (SO) potentiates opioid-induced respiratory depression (OIRD) in experiments on healthy volunteers. Our objective was to examine the relationship between SO and OIRD in patients on surgical units. Methods This post-hoc analysis utilized a portion of the observational PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) trial dataset (202 patients, two trial sites), which involved blinded continuous pulse oximetry and capnography monitoring of postsurgical patients on surgical units. OIRD incidence was determined for patients receiving room air (RA), intermittent SO, or continuous SO. Generalized estimating equation (GEE) models, with a Poisson distribution, a log-link function and time of exposure as offset, were used to compare the incidence of OIRD when patients were receiving SO vs RA. Results Within the analysis cohort, 74 patients were always on RA, 88 on intermittent and 40 on continuous SO. Compared with when on RA, when receiving SO patients had a higher risk for all OIRD episodes (incidence rate ratio [IRR] 2.7, 95% confidence interval [CI] 1.4–5.1), apnea episodes (IRR 2.8, 95% CI 1.5–5.2), and bradypnea episodes (IRR 3.0, 95% CI 1.2–7.9). Patients with high or intermediate PRODIGY scores had higher IRRs of OIRD episodes when receiving SO, compared with RA (IRR 4.5, 95% CI 2.2–9.6 and IRR 2.3, 95% CI 1.1–4.9, for high and intermediate scores, respectively). Conclusions Despite oxygen desaturation events not differing between SO and RA, SO may clinically promote OIRD. Clinicians should be aware that postoperative patients receiving SO therapy remain at increased risk for apnea and bradypnea. Trial registration Clinicaltrials.gov: NCT02811302, registered June 23, 2016.

Background: Manipulation of carcinoid tumors during ablation or selective hepatic artery embolization (transarterial embolization, TAE) can release vasoactive mediators inducing hemodynamic instability. The main aim of our study was to review hemodynamics and complications related to minimally invasive treatments of liver carcinoids with TAE or ablation. Methods: Electronic medical records of all patients with metastatic liver carcinoid undergoing ablation or TAE from 2003 to 2019 were abstracted. Noted were severe hypotension (mean arterial pressure [MAP] ..± 55.ßmmHg), severe hypertension (systolic blood pressure ... 180.ßmmHg), and perioperative complications. Associations of procedure type and pre-procedure octreotide use with intraprocedural hemodynamics were assessed using linear regression. A robust covariance approach using generalized estimating equation method was used to account for multiple observations. Results: A total of 161 patients underwent 98 ablations and 207 TAEs. Severe hypertension was observed in 24 (24.5%) vs. 15 (7.3%), severe hypotension in 56 (57.1%) vs. 6 (2.9%), and cutaneous flushing observed in 2 (2.0%) vs. 48 (23.2%) ablations and TAEs, respectively. After adjusting for preprocedural MAP, ablation was associated with lower intraprocedural MAP compared to TAE (estimate -27.ßmmHg, 95%CI -30 to -24.ßmmHg, p.ß

La polinización entomófila incrementa la calidad y la cantidad de frutos y semillas de la mayoría de los principales cultivos del mundo. San Juan es una de las principales provincias argentinas productoras de semilla hortícola; sin embargo, no se cuenta con información que permita asegurar un servicio ecosistémico de polinización óptimo a los cultivos. En este estudio se propuso determinar la influencia de la polinización entomófila en la formación de frutos y en la cantidad y calidad de las semillas de cultivos destinados a producción de semillas de achicoria, cebolla, rabanito, repollo y zapallo. Además, se evaluó si los cultivos exhibían déficit polínico en los lotes estudiados. Para ello, en cada uno de los lotes se evaluó el servicio de polinización de los cultivos a través de un experimento comparativo en el que se contrastó la formación de frutos, el número de semillas formadas por fruto, el peso y el poder germinativo de las semillas mediante diferentes tratamientos de polinización. Se encontró que la polinización entomófila actúa de manera diferencial sobre los parámetros medidos y que tiene un efecto positivo sobre la polinización de los cultivos. Además, los resultados indicaron que la formación de frutos y semillas no estuvo afectada por déficit polínico. El conocimiento alcanzado contribuye a implementar prácticas de manejo orientadas a conservar la entomofauna polinizadora, a mejorar el servicio de polinización de los cultivos y a promover la economía de los agricultores locales.

Antecedentes: La hipertensión arterial sistémica (HAS) es el principal factor de riesgo para el deterioro cognitivo; por otro lado, la memoria visuoespacial es más vulnerable al envejecimiento. Algunos fármacos antihipertensivos tienen un efecto neuroprotector, pero tal efecto puede enmascararse o bien no manifestarse por comorbilidad o por falta de control efectivo de la presión arterial. Objetivo: Evaluar las alteraciones en la memoria visuoespacial incidental de pacientes con HAS en relación con su tratamiento antihipertensivo y su control de la presión. Método: Se incluyeron 80 pacientes con HAS (46 mujeres), agrupados por su medicación en bloqueadores de los receptores de la angiotensina II (BRA) o inhibidores de la enzima convertidora de angiotensina (IECA). Se realizó un análisis de correlaciones múltiples para los puntajes obtenidos en la prueba de memoria visuoespacial incidental/intencional y un análisis de modelos mixtos (factores fijos: tratamiento, control de la presión y comorbilidad con diabetes; factores aleatorios: edad, escolaridad, meses desde el diagnóstico de HAS y coeficiente intelectual). Resultados: De los pacientes controlados, la mayoría de los que recibían BRA fueron eficientes y los que recibían IECA fueron deficientes. De los que recibían IECA, los descontrolados hipertensos fueron más eficientes que los normotensos. La memoria visuoespacial se correlacionó negativamente con la presión sistólica a pesar de no haber diferencias en MoCA y Raven. Conclusiones: La eficiencia en la memoria visuoespacial dependió de la interacción del tratamiento y el control de la presión. Ambos factores, tratamiento y control efectivo de la presión, deben considerarse en la evaluación del deterioro cognitivo asociado a la HAS.

CASZ1 is a conserved transcription factor involved in neural development, blood vessel assembly and heart morphogenesis. CASZ1 has been implicated in cancer, either suppressing or promoting tumor development depending on the tissue. However, the impact of CASZ1 on hematological tumors remains unknown. Here, we show that the T-cell oncogenic transcription factor TAL1 is a direct positive regulator of CASZ1, that T-cell acute lymphoblastic leukemia (T-ALL) samples at diagnosis overexpress CASZ1b isoform, and that CASZ1b expression in patient samples correlates with PI3K-AKT-mTOR signaling pathway activation. In agreement, overexpression of CASZ1b in both Ba/F3 and T-ALL cells leads to the activation of PI3K signaling pathway, which is required for CASZ1b-mediated transformation of Ba/F3 cells in vitro and malignant expansion in vivo. We further demonstrate that CASZ1b cooperates with activated NOTCH1 to promote T-ALL development in zebrafish, and that CASZ1b protects human T-ALL cells from serum deprivation and treatment with chemotherapeutic drugs. Taken together, our studies indicate that CASZ1b is a TAL1-regulated gene that promotes T-ALL development and resistance to chemotherapy.

Summary: The host-microbiome associations occurring on the skin of vertebrates significantly influence hosts’ health. However, the factors mediating their interactions remain largely unknown. Herein, we used integrated technical and ecological frameworks to investigate the skin metabolites sustaining a beneficial symbiosis between tree frogs and bacteria. We characterize macrocyclic acylcarnitines as the major metabolites secreted by the frogs’ skin and trace their origin to an enzymatic unbalance of carnitine palmitoyltransferases. We found that these compounds colocalize with bacteria on the skin surface and are mostly represented by members of the Pseudomonas community. We showed that Pseudomonas sp. MPFS isolated from frogs’ skin can exploit acylcarnitines as its sole carbon and nitrogen source, and this metabolic capability is widespread in Pseudomonas. We summarize frogs’ multiple mechanisms to filter environmental bacteria and highlight that acylcarnitines likely evolved for another function but were co-opted to provide nutritional benefits to the symbionts.

A Multisensory Environment (MSE) is a tool that can be used to train and stimulate the vestibular and proprioceptive systems of users, and engage them in therapeutic activities through sensors. This manuscript aims to verify the effects of an intervention protocol with MSE through a game platform to train proprioception in children with Down syndrome (CwDS). This pilot study was carried out using a system designed with the specific purpose to evaluate the children’s functional performance through data acquired using a system based on an RGB-D camera arrangement. The children underwent a physiotherapeutic intervention protocol of 12 sessions of game therapy, with 30 minutes duration each and a frequency of one session per week. This protocol was implemented to analyze the movements of three CwDS (mean of nine years old at the beginning of experiments). The CwDS evaluated in this research had an average proprioception score established by a Psychomotor profile test of ( $\text{m}=10.43$ ) before the beginning of the intervention, showing deficient and dyspraxic profiles among the children. After the application of our MSE, the final score of this test showed an average of ( $\text{m}=16.44$ ) indicating a Typical development (TD) profile for all the children.

Abstract Microbial diversity positively influences community resilience of the host microbiome. However, extinction risk factors such as habitat specialization, narrow environmental tolerances, and exposure to anthropogenic disturbance may homogenize host-associated microbial communities critical for stress responses including disease defense. In a dataset containing 43 threatened and 90 non-threatened amphibian species across two biodiversity hotspots (Brazil’s Atlantic Forest and Madagascar), we found that threatened host species carried lower skin bacterial diversity, after accounting for key environmental and host factors. The consistency of our findings across continents suggests the broad scale at which low bacteriome diversity may compromise pathogen defenses in species already burdened with the threat of extinction.

Abstract Background Host microbiomes may differ under the same environmental conditions and these differences may influence susceptibility to infection. Amphibians are ideal for comparing microbiomes in the context of disease defense because hundreds of species face infection with the skin-invading microbe Batrachochytrium dendrobatidis (Bd), and species richness of host communities, including their skin bacteria (bacteriome), may be exceptionally high. We conducted a landscape-scale Bd survey of six co-occurring amphibian species in Brazil’s Atlantic Forest. To test the bacteriome as a driver of differential Bd prevalence, we compared bacteriome composition and co-occurrence network structure among the six focal host species. Results Intensive sampling yielded divergent Bd prevalence in two ecologically similar terrestrial-breeding species, a group with historically low Bd resistance. Specifically, we detected the highest Bd prevalence in Ischnocnema henselii but no Bd detections in Haddadus binotatus. Haddadus binotatus carried the highest bacteriome alpha and common core diversity, and a modular network partitioned by negative co-occurrences, characteristics associated with community stability and competitive interactions that could inhibit Bd colonization. Conclusions Our findings suggest that community structure of the bacteriome might drive Bd resistance in H. binotatus, which could guide microbiome manipulation as a conservation strategy to protect diverse radiations of direct-developing species from Bd-induced population collapses.

Rationale Post-coronavirus disease 2019 (COVID-19) survivors frequently have dyspnoea that can lead to exercise intolerance and lower quality of life. Despite recent advances, the pathophysiological mechanisms of exercise intolerance in the post-COVID-19 patients remain incompletely characterised. The objectives of the present study were to clarify the mechanisms of exercise intolerance in post-COVID-19 survivors after hospitalisation. Methods This prospective study evaluated consecutive patients previously hospitalised due to moderate-to-severe/critical COVID-19. Within mean±sd 90±10 days of onset of acute COVID-19 symptoms, patients underwent a comprehensive cardiopulmonary assessment, including cardiopulmonary exercise testing with earlobe arterialised capillary blood gas analysis. Measurements and main results 87 patients were evaluated; mean±sd peak oxygen consumption was 19.5±5.0 mL·kg−1·min−1, and the tertiles were ≤17.0, 17.1–22.2 and ≥22.3 mL·kg−1·min−1. Hospitalisation severity was similar among the three groups; however, at the follow-up visit, patients with peak oxygen consumption ≤17.0 mL·kg−1·min−1 reported a greater sensation of dyspnoea, along with indices of impaired pulmonary function, and abnormal ventilatory, gas-exchange and metabolic responses during exercise compared to patients with peak oxygen consumption >17 mL·kg−1·min−1. By multivariate logistic regression analysis (receiver operating characteristic curve analysis) adjusted for age, sex and prior pulmonary embolism, a peak dead space fraction of tidal volume ≥29 and a resting forced vital capacity ≤80% predicted were independent predictors of reduced peak oxygen consumption. Conclusions Exercise intolerance in the post-COVID-19 survivors was related to a high dead space fraction of tidal volume at peak exercise and a decreased resting forced vital capacity, suggesting that both pulmonary microcirculation injury and ventilatory impairment could influence aerobic capacity in this patient population.

Despite long-term sequelae of COVID-19 are emerging as a substantial public health concern, the mechanism underlying these processes still unclear. Evidence demonstrates that SARS-CoV-2 Spike protein can reach different brain regions, irrespective of viral brain replication resulting in activation of pattern recognition receptors (PRRs) and neuroinflammation. Considering that microglia dysfunction, which is regulated by a whole array of purinergic receptors, may be a central event in COVID-19 neuropathology, we investigated the impact of SARS-CoV-2 Spike protein on microglial purinergic signaling. Here, we demonstrate that cultured microglial cells (BV2 line) exposed to Spike protein induce ATP secretion and upregulation of P2Y6, P2Y12, NTPDase2 and NTPDase3 transcripts. Also, immunocytochemistry analysis shows that spike protein increases the expression of P2X7, P2Y1, P2Y6, and P2Y12 in BV2 cells. Additional, hippocampal tissue of Spike infused animals (6,5ug/site, i.c.v.) presents increased mRNA levels of P2X7, P2Y1, P2Y6, P2Y12, NTPDase1, and NTPDase2. Immunohistochemistry experiments confirmed high expression of the P2X7 receptor in microglial cells in CA3/DG hippocampal regions after spike infusion. These findings suggest that SARS-CoV-2 Spike protein modulates microglial purinergic signaling and opens new avenues for investigating the potential of purinergic receptors to mitigate COVID-19 consequences.

Abstract Background There is a lack of studies that assess the effectiveness of pharmacotherapeutic follow-up in the context of the judicialization of insulin analogues. Aims To evaluate the clinical and humanistic impact of pharmacotherapeutic follow-up in patients with type 1 diabetes mellitus who receive insulin analogues by judicial decision in a Brazilian municipality. Methods A quasi-experimental study of the before-and-after type was carried out through pharmacotherapeutic follow-up. Patients who accepted to participate in the study underwent laboratory tests of glycemic and lipid profile before and after the intervention, and underwent five pharmaceutical consultations. In addition, quality of life and health, knowledge, and skills related to insulin application techniques were analyzed. Results 28 patients participated in all stages. Of these, most were female (53.6%), with a mean age of 32.8 ± 11.6 years. After the intervention, there was a reduction in blood glucose levels, blood pressure, and increased body mass index. In addition, there was greater knowledge and skills regarding insulin application techniques, improved quality of life, health, greater number of medications used, reduction of pharmacotherapeutic problems, and improvement in eating habits. Conclusion The pharmacotherapeutic follow-up promoted clinical and humanistic benefits, with improvement in quality of life and health.

Introduction: The outcomes regarding portal hypertension-related complications and infections after HCV cure in decompensated cirrhosis are scarcely reported. We aimed to identify the predictors of survival and to evaluate the frequency of decompensation events of cirrhosis, including hepatocellular carcinoma (HCC), portal hypertension complications and infections in a cohort of decompensated cirrhotic with sustained virological response (SVR) in a real-world scenario. Patients and methods: This was a prospective study in consecutive HCV-infected patients with decompensated cirrhosis who achieved SVR after direct-acting antiviral (DAA) treatment. At baseline, clinical and laboratory data were recorded. Patients were followed until development of outcomes regarding further decompensation, death, or liver transplant. A Cox-regression analysis was performed and survival curves were constructed using the Kaplan Mayer method. Results: One hundred and thirty patients (age 60 ± 9 years, 64% female, 70% genotype 1) were included and followed-up through three years. SVR was associated with a lower prevalence of ascites and an improvement in Child-Pugh and MELD scores. One and three-year probability of transplant-free survival was 93% and 66%, respectively. Variables related to three-years survival were MELD < 11 (HR 1.24, 95% CI 1.13-1.37) and absence of ascites (HR 2.03, 95% CI 0.99-4.13) after the end of treatment (91% versus 37% in patients with ascites and a higher MELD, p

The impact of sexual dimorphism on facial attractiveness has been controversial owing to contradictory results, particularly in studies on female preferences. Given that sexually dimorphic facial features, especially more masculine ones, have been previously related to the perception of anger, we investigated the bi-directional influence of emotional expressions and facial masculinity and explored their impact on women's preferences for facial masculinity. We confirmed the effect of facial sexual dimorphism on the perception of emotional cues (happiness and anger) and explored whether smiling or angry expressions influence women's perception of masculinity in male faces. Additionally, we examined women's preferences for emotionally expressive male faces altered along a continuum of masculinity. The results showed that masculinised faces are perceived as angrier, while feminised faces are perceived as happier (Experiment 1), and that angry faces are perceived as more masculine when compared with happy faces (Experiment 2). It is noteworthy that our Experiment 3 uncovered a pivotal finding: women prefer reduced feminisation in happy faces compared with neutral/angry faces. This suggests that the avoidance response observed towards masculinity is attenuated by a smiling expression. The current study introduces a new perspective to be considered when exploring the role of facial masculinity in women's attractiveness preferences.

BackgroundCardiac magnetic resonance (CMR) global longitudinal strain and circumferential strain abnormalities have been associated with left ventricular ejection fraction (LVEF) reduction and cardiotoxicity from oncologic therapy. However, few studies have evaluated the associations of strain and cardiovascular outcomes.ObjectivesTo assess CMR circumferential and global longitudinal strain (GLS) correlations with cardiovascular outcomes including myocardial infarction, systolic dysfunction, diastolic dysfunction, arrhythmias and valvular disease in breast cancer patients treated with and without anthracyclines and/or trastuzumab therapy.MethodsBreast cancer patients with a CMR from 2013-2017 at Yale New Haven Hospital were included. Patient co-morbidities, medications, and cardiovascular outcomes were obtained from chart review. Biostatistical analyses, including Pearson correlations, competing risk regression model, and competing risk survival curves comparing the two groups were analyzed.Results116 breast cancer with CMRs were included in our analysis to assess differences between Anthracycline/Trastuzumab (AT) (62) treated versus non anthracycline/trastuzumab (NAT) (54) treated patients in terms of imaging characteristics and outcomes. More AT patients 17 (27.4%) developed systolic heart failure compared to the NAT group 6 (10.9%), p = 0.025. Statin use was associated with a significant reduction in future arrhythmias (HR 0.416; 95% CI 0.229-0.755, p = 0.004). In a sub-group of 13 patients that underwent stress CMR, we did not find evidence of microvascular dysfunction by sub-endocardial/sub-epicardial myocardial perfusion index ratio after adjusting for ischemic heart disease.ConclusionsIn our study, CMR detected signs of subclinical cardiotoxicity such as strain abnormalities despite normal LV function and abnormal circumferential strain was associated with adverse cardiovascular outcomes such as valvular disease and systolic heart failure. Thus, CMR is an important tool during and after cancer treatment to identity and prognosticate cancer treatment-related cardiotoxicity.

Interleukin-7 receptor alpha (IL7Ra) is important for lymphoid cell development but its role in leukaemogenesis is not clear. Here, the authors generate a knock-in murine model to show that activating mutations in IL7Ra can initiate precursor B-cell acute lymphoblastic leukaemia.

Free-living microturbellarians are a part of lentic and lotic aquatic assemblages and play an important but underestimated role in aquatic ecosystems. Consequently, they are not included in studies on the dynamics of freshwater aquatic invertebrate communities. We report eight new records of microturbellarians from the Suquía River (Córdoba, Argentina): Catenula lemnae Dugès, 1832, Stenostomum arevaloi Gieysztor, 1931, Stenostomum aff. amphotum Marcus, 1945, Macrostomum aff. quiritium Beklemischev, 1951, Macrostomum platensis Adami, Damborenea & Ronderos, 2012, Microstomum sp., and Mesostoma erhenbergii (Focke, 1836). We discuss these results within the geomorphological history of the river basin

Abstract Background Self-limited Childhood Epilepsies are the most prevalent epileptic syndrome in children. Its pathogenesis is unknown. In this disease, symptoms resolve spontaneously in approximately 50% of patients when maturity is reached, prompting to a maturation problem. The purpose of this study was to understand the molecular bases of this disease by generating and analyzing induced pluripotent stem cell-derived neurons from a family with 7 siblings, among whom 4 suffer from this disease. Methods Two affected siblings and, as controls, a healthy sister and the unaffected mother of the family were studied. Using exome sequencing, a homozygous variant in the FYVE, RhoGEF and PH Domain Containing 6 gene was identified in the patients as a putative genetic factor that could contribute to the development of this familial disorder. After informed consent was signed, skin biopsies from the 4 individuals were collected, fibroblasts were derived and reprogrammed and neurons were generated and characterized by markers and electrophysiology. Morphological, electrophysiological and gene expression analyses were performed on these neurons. Results Bona fide induced pluripotent stem cells and derived neurons could be generated in all cases. Overall, there were no major shifts in neuronal marker expression among patient and control-derived neurons. Compared to two familial controls, neurons from patients showed shorter axonal length, a dramatic reduction in synapsin-1 levels and cytoskeleton disorganization. In addition, neurons from patients developed a lower action potential threshold with time of in vitro differentiation and the amount of current needed to elicit an action potential (rheobase) was smaller in cells recorded from NE derived from patients at 12 weeks of differentiation when compared with shorter times in culture. These results indicate an increased excitability in patient cells that emerges with the time in culture. Finally, functional genomic analysis showed a biased towards immaturity in patient-derived neurons. Conclusions We are reporting the first in vitro model of self-limited childhood epilepsy, providing the cellular bases for future in-depth studies to understand its pathogenesis. Our results show patient-specific neuronal features reflecting immaturity, in resonance with the course of the disease and previous imaging studies.

Artificial insemination using cooled-transported semen has marked importance in equine breeding programs around the world, and the high value of mules has generated avid interest in donkey semen biotechnology. However, donkey semen cools poorly in commercially available equine extenders. Therefore, this study aimed to develop approaches to improve the ability of donkey semen to tolerate cooling. Ejaculates of seven donkeys (n = 21) were cooled at 5°C for 48 h in three different extenders (milk-based, SM; sodium caseinate-based, SC; or egg yolk-based, EY) in the presence or absence of seminal plasma (centrifugation, C). Sperm motility, plasma membrane integrity (PMI), plasma membrane stability (PMS), mitochondrial membrane potential (HMMP), intracellular hydrogen peroxide (H2O2), and intracellular superoxide (O2−) were assessed before, 24 h, and 48 h post-cooling. In addition, 15 mares (163 estrous cycles) were randomly inseminated with semen from two jacks (Jack 1, n = 90; Jack 2, n = 73) previously cooled for 24 h under one of the treatments (SM, SC, EY, SM-C, SC-C, or EY-C). Groups EY, SC-C, and EY-C (P < 0.05) demonstrated superior sperm analytical parameters to SM at 24 and 48 h. Centrifugation positively affected sperm analytical parameters in cooled donkey semen extended in SM and SC (P < 0.05). Mares bred with semen extended in SC (67%, 18/27), SC-C (89%, 24/27), EY (89%, 25/28), or EY-C (74%, 20/27) had significantly greater conception rates than mares bred with SM (33%, 9/27; P < 0.05). Mares bred with SM-C had intermediate conception rates (59%, 16/27). In conclusion, SC and EY improved the cooling ability and fertility of donkey semen in horse mares, and centrifugation positively affected donkey semen extended in SM.

By-products from fruit industrialization retain nutritional and functional components; thus, they may find use in animal feeding. This study aimed to assess the effects of dietary fruit industrial by-products on the tilapias blood biochemical and oxidative parameters and on the composition and lipid peroxidation of their fillets. Four diets were supplied to the tilapias: a C-control diet, with no fruit meal, and three diets containing 5% of either acerola (ACM), apple (APM) or grape (GRM) meal. The phenolic compounds and the carotenoids in the meals and their antioxidant capacities were measured. Fish were weighed and measured for the calculation of the growth performance data, their blood was analyzed for health and oxidative status biomarkers and their fillets were analyzed for proximal composition and lipid peroxidation. Grape meal had the highest concentration of phenolics and carotenoids and the highest antioxidant activity, followed by acerola and apple meals. The productive performance was similar among the treatments. The fruit by-product diets either maintained or improved the biochemical biomarkers of health and improved the oxidative status of the fish. The fruit by-product diets increased the concentration of lipids in the fillets and slowed down the onset of the lipid peroxidation during frozen storage.

Abstract The host‐associated microbiome plays a significant role in health. However, the roles of factors such as host genetics and microbial interactions in determining microbiome diversity remain unclear. We examined these factors using amplicon‐based sequencing of 175 Thoropa taophora frog skin swabs collected from a naturally fragmented landscape in southeastern Brazil. Specifically, we examined (1) the effects of geography and host genetics on microbiome diversity and structure; (2) the structure of microbial eukaryotic and bacterial co‐occurrence networks; and (3) co‐occurrence between microeukaryotes with bacterial OTUs known to affect growth of the fungal pathogen Batrachochytrium dendrobatidis (Bd). While bacterial alpha diversity varied by both site type and host MHC IIB genotype, microeukaryotic alpha diversity varied only by site type. However, bacteria and microeukaryote composition showed variation according to both site type and host MHC IIB genotype. Our network analysis showed the highest connectivity when both eukaryotes and bacteria were included, implying that ecological interactions may occur among domains. Lastly, anti‐Bd bacteria were not broadly negatively co‐associated with the fungal microbiome and were positively associated with potential amphibian parasites. Our findings emphasize the importance of considering both domains in microbiome research and suggest that for effective probiotic strategies for amphibian disease management, considering potential interactions among all members of the microbiome is crucial.

IntroductionSevere acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) infection triggers inflammatory clinical stages that affect the outcome of patients with coronavirus disease 2019 (COVID-19). Disease severity may be associated with a metabolic imbalance related to amino acids, lipids, and energy-generating pathways. The aim of this study was to characterize the profile of amino acids and acylcarnitines in COVID-19 patients. A multicenter, cross-sectional study was carried out. A total of 453 individuals were classified by disease severity. Levels of 11 amino acids, 31 acylcarnitines, and succinylacetone in serum samples were analyzed by electrospray ionization–triple quadrupole tandem mass spectrometry. Different clusters were observed in partial least squares discriminant analysis, with phenylalanine, alanine, citrulline, proline, and succinylacetone providing the major contribution to the variability in each cluster (variable importance in the projection >1.5). In logistic models adjusted by age, sex, type 2 diabetes mellitus, hypertension, and nutritional status, phenylalanine was associated with critical outcomes (odds ratio=5.3 (95% CI 3.16-9.2) in the severe vs. critical model, with an area under the curve of 0.84 (95% CI 0.77-0.90). In conclusion the metabolic imbalance in COVID-19 patients might affect disease progression. This work shows an association of phenylalanine with critical outcomes in COVID-19 patients, highlighting phenylalanine as a potential metabolic biomarker of disease severity.

Abstract Climate has a large impact on diversity and evolution of the world’s biota. The Eocene–Oligocene transition from tropical climate to cooler, drier environments was accompanied by global species turnover. A large number of Old World lacertid lizard lineages have diversified after the Eocene–Oligocene boundary. One of the most speciose reptile genera in the arid Palearctic, Acanthodactylus, contains two sub-Saharan species with unresolved phylogenetic relationship and unknown climatic preferences. We here aim to understand how and when adaptation to arid conditions occurred in Acanthodactylus and when tropical habitats where entered. Using whole mitogenomes from fresh and archival DNA and published sequences we recovered a well-supported Acanthodactylus phylogeny and underpinned the timing of diversification with environmental niche analyses of the sub-Saharan species A. guineensis and A. boueti in comparison to all arid Acanthodactylus. We found that A. guineensis represents an old lineage that splits from a basal node in the Western clade, and A. boueti is a derived lineage and probably not its sister. Their long branches characterize them—and especially A. guineensis—as lineages that may have persisted for a long time without further diversification or have undergone multiple extinctions. Environmental niche models verified the occurrence of A. guineensis and A. boueti in hot humid environments different from the other 42 arid Acanthodactylus species. While A. guineensis probably remained in tropical habitat from periods prior to the Eocene–Oligocene boundary, A. boueti entered tropical environments independently at a later period. Our results provide an important baseline for studying adaptation and the transition from humid to arid environments in Lacertidae.

Resumo Fundamento A doença de Chagas (DC) constitui uma causa potencial negligenciada de doença microvascular coronariana (DMC). Objetivos Comparar pacientes com DMC relacionada à DC (DMC-DC) com pacientes com DMC ligada a outras etiologias (DMC-OE). Métodos De 1292 pacientes estáveis, encaminhados para angiografia coronária invasiva para elucidar o padrão hemodinâmico e a causa de angina, 247 apresentaram coronárias subepicárdicas normais, e 101 foram incluídos após aplicação dos critérios de exclusão. Desses, 15 compuseram o grupo de DMC-DC e suas características clínicas, hemodinâmicas, angiográficas, e cintilográficas foram comparadas às do grupo de 86 pacientes com DMC-OE. O nível de significância estatística para todas as comparações adotado foi de 0,05. Resultados Pacientes com suspeita de DMC-DC apresentaram características antropométricas, clínicas e angiográficas, além de alterações hemodinâmicas e de perfusão miocárdica estatisticamente comparáveis às detectadas nos 86 pacientes com DMC-OE. Disfunção ventricular diastólica, expressa por elevada pressão telediastólica do ventrículo esquerdo, foi igualmente encontrada nos dois grupos. Entretanto, em comparação a esse grupo com DMC-OE, o grupo com DMC-DC exibiu fração de ejeção ventricular esquerda mais baixa (61,1 ± 11,9 vs 54,8 ± 15,9; p= 0,049) e mais elevado escore de mobilidade da parede ventricular (1,77 ± 0,35 vs 1,18 ± 0,26; p= 0,02). Conclusão A cardiomiopatia crônica da doença de Chagas esteve associada à etiologia de possível doença microvascular coronariana em 15% de amostra de 101 pacientes estáveis, cujo sintoma principal era angina requerendo elucidação por angiografia invasiva. Embora os grupos DMC-DC e DMC-OE apresentassem características clínicas, hemodinâmicas, e de perfusão miocárdica em comum, a disfunção global e segmentar do ventrículo esquerdo foi mais grave nos pacientes com DMC associada à DC em comparação à DMC por outras etiologias. (Arq Bras Cardiol. 2020; 115(6):1094-1101)

Abstract In Brazil’s Atlantic Forest (AF) biodiversity conservation is of key importance since the fungal pathogen Batrachochytrium dendrobatidis (Bd) has led to the rapid loss of amphibian populations here and worldwide. The impact of Bd on amphibians is determined by the host's immune system, of which the skin microbiome is a critical component. The richness and diversity of such cutaneous bacterial communities are known to be shaped by abiotic factors which thus may indirectly modulate host susceptibility to Bd. This study aimed to contribute to understanding the environment-host–pathogen interaction determining skin bacterial communities in 819 treefrogs (Anura: Hylidae and Phyllomedusidae) from 71 species sampled across the AF. We investigated whether abiotic factors influence the bacterial community richness and structure on the amphibian skin. We further tested for an association between skin bacterial community structure and Bd co-occurrence. Our data revealed that temperature, precipitation, and elevation consistently correlate with richness and diversity of the skin microbiome and also predict Bd infection status. Surprisingly, our data suggest a weak but significant positive correlation of Bd infection intensity and bacterial richness. We highlight the prospect of future experimental studies on the impact of changing environmental conditions associated with global change on environment-host–pathogen interactions in the AF.

Objectives: This study examined the trajectory of perinatal depressive symptoms in Portuguese women during the COVID-19 pandemic and the role of individual, relational, and contextual risk and protective factors.Methods: This 3-wave longitudinal study followed 290 pregnant women from the third trimester of pregnancy until 6-months postpartum. Women self-reported on depressive symptoms, psychological (anxiety, perceived stress, mindfulness), relational (perceived social support, dyadic adjustment, sexual wellbeing), and contextual (lockdown status) factors.Results: Women who were under strict lockdown presented significantly higher scores of depressive symptoms at baseline (by 1.38 EPDS points) than women who were not under strict lockdown measures. Mixed Growth Models showed that trajectories of depressive symptoms were explained by differences in women’s baseline depression. Differences in women’s depressive symptoms at baseline were mainly explained by higher anxiety and lower social support (22% and 24% for women under lockdown; 39% and 6% for women not on lockdown, respectively).Conclusion: Preventative interventions targeted at pregnant women should aim to reduce anxiety and enhance women’s social support to prevent depression in pregnancy and postpartum during the COVID-19 pandemic.

Cancer mortality has improved due to earlier detection via screening, as well as due to novel cancer therapies such as tyrosine kinase inhibitors and immune checkpoint inhibitions. However, similarly to older cancer therapies such as anthracyclines, these therapies have also been documented to cause cardiotoxic events including cardiomyopathy, myocardial infarction, myocarditis, arrhythmia, hypertension, and thrombosis. Imaging modalities such as echocardiography and magnetic resonance imaging (MRI) are critical in monitoring and evaluating for cardiotoxicity from these treatments, as well as in providing information for the assessment of function and wall motion abnormalities. MRI also allows for additional tissue characterization using T1, T2, extracellular volume (ECV), and delayed gadolinium enhancement (DGE) assessment. Furthermore, emerging technologies may be able to assist with these efforts. Nuclear imaging using targeted radiotracers, some of which are already clinically used, may have more specificity and help provide information on the mechanisms of cardiotoxicity, including in anthracycline mediated cardiomyopathy and checkpoint inhibitor myocarditis. Hyperpolarized MRI may be used to evaluate the effects of oncologic therapy on cardiac metabolism. Lastly, artificial intelligence and big data of imaging modalities may help predict and detect early signs of cardiotoxicity and response to cardioprotective medications as well as provide insights on the added value of molecular imaging and correlations with cardiovascular outcomes. In this review, the current imaging modalities used to assess for cardiotoxicity from cancer treatments are discussed, in addition to ongoing research on targeted molecular radiotracers, hyperpolarized MRI, as well as the role of artificial intelligence (AI) and big data in imaging that would help improve the detection and prognostication of cancer-treatment cardiotoxicity.

The mitogenome of the South American parthenogenetic lizard Loxopholis percarinatum Müller, 1923 (Squamata: Gymnophthalmidae), a uni-bisexual species complex, was recovered for three individuals from Rio Negro region, Amazonas, Brazil. The content and order of genes are typical for vertebrate mitochondrial genomes, and we recovered 13 protein-coding genes, 22 tRNA, and two rRNA (12S and 16S), in addition to partial fragments of the Control Region. A maximum likelihood phylogenetic analysis with mitogenomes of selected lizard families recovered L. percarinatum with Iphisa elegans Gray, 1851, the only other Gymnophthalmidae species available in GenBank.

Genetic variants in KIF3A are associated with atopic dermatitis (AD). Here, the authors identify two AD-risk alleles that show high methylation resulting in lower KIF3A expression. Mice with epidermis-specific loss of Kif3a show disrupted skin barrier homeostasis and increased AD susceptibility.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic, affecting more than 219 countries and causing the death of more than 5 million people worldwide. The genetic background represents a factor that predisposes the way the host responds to SARS-CoV-2 infection. In this sense, genetic variants of ACE and ACE2 could explain the observed interindividual variability to COVID-19 outcomes. In order to improve the understanding of how genetic variants of ACE and ACE2 are involved in the severity of COVID-19, we included a total of 481 individuals who showed clinical manifestations of COVID-19 and were diagnosed by reverse transcription PCR (RT-PCR). Genomic DNA was extracted from peripheral blood and saliva samples. ACE insertion/deletion polymorphism was evaluated by the high-resolution melting method; ACE single-nucleotide polymorphism (SNP) (rs4344) and ACE2 SNPs (rs2285666 and rs2074192) were genotyped using TaqMan probes. We assessed the association of ACE and ACE2 polymorphisms with disease severity using logistic regression analysis adjusted by age, sex, hypertension, type 2 diabetes, and obesity. The severity of the illness in our study population was divided as 31% mild, 26% severe, and 43% critical illness; additionally, 18% of individuals died, of whom 54% were male. Our results showed in the codominant model a contribution of ACE2 gene rs2285666 T/T genotype to critical outcome [odds ratio (OR) = 1.83; 95%CI = 1.01–3.29; p = 0.04] and to require oxygen supplementation (OR = 1.76; 95%CI = 1.01–3.04; p = 0.04), in addition to a strong association of the T allele of this variant to develop critical illness in male individuals (OR = 1.81; 95%CI = 1.10–2.98; p = 0.02). We suggest that the T allele of rs2285666 represents a risk factor for severe and critical outcomes of COVID-19, especially for men, regardless of age, hypertension, obesity, and type 2 diabetes.

Cruzain, the main cysteine protease of Trypanosoma cruzi, plays key roles in all stages of the parasite’s life cycle, including nutrition acquisition, differentiation, evasion of the host immune system, and invasion of host cells. Thus, inhibition of this validated target may lead to the development of novel drugs for the treatment of Chagas disease. In this study, a multiparameter optimization (MPO) approach, molecular modeling, and structure-activity relationships (SARs) were employed for the identification of new benzimidazole derivatives as potent competitive inhibitors of cruzain with trypanocidal activity and suitable pharmacokinetics. Extensive pharmacokinetic studies enabled the identification of metabolically stable and permeable compounds with high selectivity indices. CYP3A4 was found to be involved in the main metabolic pathway, and the identification of metabolic soft spots provided insights into molecular optimization. Compound 28, which showed a promising trade-off between pharmacodynamics and pharmacokinetics, caused no acute toxicity and reduced parasite burden both in vitro and in vivo.

Background: Coccidiosis is the infectious disease with the greatest economic impact in poultry production. Additionally, chemotherapeutic growth promoters are being substituted for safer alternative strategies. Objective: To evaluate the effect of feeding oleoresins from chili pepper (Capsicum annuum) and turmeric (Curcuma longa L.) on the performance, survival rate, and the Productive Efficiency Index of broilers from 1 to 21d challenged by Eimeria sp. Methods: A total of 700 male 1-dayold chicks (Cobb 500) challenged with Eimeria sp, were assigned to a completely randomized design with four treatments: (1) negative control diet, without anticoccidial agent or growth promoters; (2) control diet+0.05% salinomycin; (3) negative control diet+100g/ton; and (4) negative control diet +140g/ton of test product (Curcuma longa L. plus Capsicum annuum oleoresins). Results: Body weight, weight gain, feed conversion and Productive Efficiency Index did not differ between broilers fed anticoccidial chemotherapeutics and oleoresins. In addition, there was no difference in feed intake and survival rate between dietary treatments. Conclusion: Broilers supplemented with chili pepper and turmeric oleoresins from 1 to 21d present similar body weight, weight gain, feed conversion, and Productive Efficiency Index compared to broilers supplemented with chemotherapeutic anticoccidials without affecting feed intake or survival rate.

Detrimental biopsychosocial effects of the COVID-19 pandemic on populations have been established worldwide. Despite research indicating that the transition to parenthood is a vulnerable period for maternal and paternal health, an in-depth examination of the specific challenges the pandemic poses for new mothers and fathers is still lacking. Using a mixed-method design, we investigated individual and relational well-being of women and men who were expecting their first child during the first months of the COVID-19 pandemic in Portugal and its associations with contextual, individual, and relational factors. Adults older than 18 (n = 316, 198 women) from early pregnancy to 6-months postpartum completed a cross-sectional online survey assessing sociodemographic, individual (depression, anxiety, perceived stress), and relational (dyadic adjustment, perceived social support) self-report measures. From those, 99 participants (64 women) responded to an open-ended question and reported perceived changes in their couple’s relationship due to the pandemic. Men responding during strict lockdown measures reported significantly higher levels of perceived stress relative to those men who were not under lockdown. Overall, women reported higher levels of depression and greater social support than men. Qualitative analyses resulted in two main themes: Individual Changes and Relational Changes. These themes aggregate personal concerns and experiences (e.g., worsening of mental health, uncertainty about the future, lack of freedom) interrelated with relational issues (e.g., increased togetherness, avoidance of physical contact, and increased availability for parenthood during lockdown). The prevalence of negative effects (58.6%) exceeded the described positive effects (28.3%), and 13.1% described both positive and negative effects of the pandemic. Current findings offer grounds for important evidence-based strategies to mitigate the potential adverse effects of the current pandemic on new mothers’ and fathers’ individual and relational well-being.

In The Portuguese Empire, 1415-1808: A World on the Move, A.J.R. Russell-Wood notes that the expansion and workings of Portugal’s early modern empire were the product of Portuguese male migration and settlement in Asia, Africa, and the Americas. But he reminds us that this history owes much to the intra and intercontinental movement of people, both voluntary and coerced, that Portugal promoted. The resulting population of mixed European and indigenous or African descent, who were encouraged or forced to embrace Portuguese laws and practices when conducting their affairs, created the political and cultural coherence that supported Portugal’s imperial claims and aspirations. This article will engage with Russell-Wood’s insight into the human and intimate foundations of empire through a local history of the town of Sabará. It explores the trajectory of various mixed – African and Portuguese – households to examine the impact their economic activities, interpersonal dynamics, and experiences with slavery and freedom had on the development of that corner of the Portuguese World. Moreover, it looks beyond white men to center its narrative on the African and African descendant women whose labor, exploitation, and pursuit of freedom supported the various historical processes that ultimately advanced Portugal’s imperial interests.

Damage caused by wildlife is one reason preventing peaceful coexistence between humans and wildlife. To identify the complexity and scope of human-wildlife interactions and to guide conservation interventions, a theoretical framework has been recently proposed, based on the field of conflict analysis and peacebuilding. Despite its importance, to our knowledge, there are no studies yet testing the framework. We therefore adapted and expanded the framework to investigate a wildlife-people interaction scenario, involving damage by giant armadillos (Priodontes maximus) to apiaries in the Brazilian Cerrado biome of Mato Grosso do Sul state. From August to November 2018, we interviewed 111 beekeepers identified through a mixed random and snowball sampling design to assess at which level of conflict this interaction could be framed, and to identify strategies able to promote coexistence. Analysis of the five key areas of the framework suggested the current human-wildlife interaction is a level one conflict. This means the negative relation between beekeepers and giant armadillos is still not rooted in less visible, more complex social disagreements, but founded in a material dispute: destruction of beehives. We used the findings to create an intervention strategy which involves: (i) the implementation of mitigation strategies that prevent giant armadillos from predating beehives; (ii) a certification scheme to acknowledge beekeepers' efforts to implement the mitigation strategies, and (iii) a Citizen Science Program using an app that enables data gathering for adaptive management, as well as maintains beekeeper engagement. We hope beekeepers-giant armadillos' coexistence will become beneficial rather than a challenge with the novel interventions.

Study objectives: Mogamulizumab is an important treatment for T-cell leukemia and lymphoma. Adverse cardiovascular events (ACE) after mogamulizumab therapy have not been investigated. The aim of the study is to investigate ACE occurrence after mogamulizumab therapy. Methods: The International World Health Organization database, VigiBase, was analyzed from January 2013 to August 2019 for all adverse events, including ACE, that occurred after mogamulizumab treatment. ACE was defined as: cardiac death, myocardial infarction, heart failure, myocarditis, arrhythmia, vasculitis, thrombosis, palpitations and new hypertension. Results: ACE after mogamulizumab therapy affected 28 out of 650 unique patients (4.3%). Heart failure (42.8%) and ventricular arrhythmias (17.85%) were most common. ACE accounted for 10% of all fatal adverse outcomes, and 25% of all ACE were fatal. Time to fatal outcome was significantly shorter for patients with ACE compared to non-cardiovascular events, with a mean of 7.7 days (SD 6.91) vs 73 days (SD 90.7), p = 0.017, respectively. There was an increased total number of adverse cardiovascular events in patients greater than 65 and in Asian countries. Conclusions: Cardiovascular toxicity with mogamulizumab is a possible early occurring adverse outcome associated with high mortality.

The purpose of this paper was to systematically summarize the published literature on neonatal isolated hyperthyrotropinemia (HTT), with a focus on prevalence, L-T4 management, re-evaluation of thyroid function during infancy or childhood, etiology including genetic variation, thyroid imaging tests, and developmental outcome. Electronic and manual searches were conducted for relevant publications, and a total of 46 articles were included in this systematic review. The overall prevalence of neonatal HTT was estimated at 0.06%. The occurrence of abnormal imaging tests was found to be higher in the persistent than in the transient condition. A continuous spectrum of thyroid impairment severity can occur because of genetic factors, environmental factors, or a combination of the two. Excessive or insufficient iodine levels were found in 46% and 16% of infants, respectively. Thirty-five different genetic variants have been found in three genes in 37 patients with neonatal HTT of different ethnic backgrounds extracted from studies with variable design. In general, genetic variants reported in the TSHR gene, the most auspicious candidate gene for HTT, may explain the phenotype of the patients. Many practitioners elect to treat infants with HTT to prevent any possible adverse developmental effects. Most patients with thyroid abnormalities and/or carrying monoallelic or biallelic genetic variants have received L-T4 treatment. For all those neonates on treatment with L-T4, it is essential to ensure follow-up until 2 or 3 years of age and to conduct medically supervised trial-off therapy when warranted. TSH levels were found to be elevated following cessation of therapy in 44% of children. Withdrawal of treatment was judged as unsuccessful, and medication was restarted, in 78% of cases. Finally, data extracted from nine studies showed that none of the 94 included patients proved to have a poor developmental outcome (0/94). Among subjects presenting with normal cognitive performance, 82% of cases have received L-T4 therapy. Until now, the precise neurodevelopmental risks posed by mild disease remain uncertain.

Introducción: la pandemia de COVID-19 impone a los profesionales de la salud: altas exigencias y modificaciones en el modo de vincularse con pacientes, pares y familiares. Estos cambios implican consecuencias emocionales tales como el incremento del nivel de estrés y síntomas de ansiedad y de depresión. Objetivo: describir un proyecto interdisciplinario creado bajo el modelo de la Medicina Narrativa dirigido a habilitar el relato de la experiencia de profesionales de la salud pertenecientes a un hospital general privado de alta complejidad de la ciudad de Buenos Aires durante la pandemia de COVID-19. Metodología: se creó una lista de correo y se convocó a profesionales del hospital a realizar una producción escrita, oral o gráfica que represente su experiencia durante la pandemia. Luego, el material recibido se envió a la misma lista de distribución con frecuencia semanal. En cada correo se renovó la invitación a narrar lo vivido o comentar los relatos de otros. Resultados: en el transcurso de siete semanas se recibieron diez producciones individuales: ocho textos, un audio y un gráfico. Los principales temas tratados pudieron agruparse en tres ejes: sala COVID, comunidad y telemedicina. Los autores fueron profesionales de Medicina, Enfermería, Psicología y de Puericultura. Conclusión: desarrollamos un proyecto bajo el modelo de la Medicina Narrativa que permitió a profesionales narrar su experiencia durante la pandemia de COVID-19, habilitando la posibilidad de poner en palabras lo vivido, reflexionar sobre modelos de actuación y elaborar el desgaste emocional generado por el contacto permanente con el dolor y el sufrimiento.

To investigate if sex-specific physiologic characteristics could impact postoperative respiratory depression risks in women, we studied incidence and risk factors associated with postoperative respiratory depression in a gynecologic surgical cohort. Only hysterectomies performed under general anesthesia from 2012 to 2017 were included to minimize interprocedural variability. Respiratory depression was defined as episodes of apnea, hypopnea, hypoxemia, pain-sedation mismatch, unplanned positive airway pressure device application, or naloxone administration in the post-anesthesia care unit. Multivariable logistic regression was used to explore the association with clinical characteristics. From 1,974 hysterectomies, 253 had postoperative respiratory depression, yielding an incidence of 128 (95% confidence interval, 114–144) per 1,000 surgeries. Risk factors associated with respiratory depression were older age (odds ratio 1.22 [95% confidence interval 1.02–1.46] per decade increase, p = 0.03), lower body weight (0.77 [0.62–0.94] per 10 kg/m2, p = 0.01), and higher intraoperative opioid dose (1.05 [1.01–1.09] per 10 mg oral morphine equivalents, p = 0.01); while sugammadex use was associated with a reduced risk (0.48 [0.30–0.75], p = 0.002). Respiratory depression was not associated with increased hospital stay, postoperative complications, or mortality. Postoperative respiratory depression risk in women increased with age, lower weight, and higher intraoperative opioids and decreased with sugammadex use; however, it was not associated with postoperative pulmonary complications.

Background: The cost of feed in fish farming can exceed 70% of the total costs. Thus, the feed industry have sought to formulate balanced diets including low-cost by-products. Objective: To evaluate sunflower meal as a partial substitute (0, 10, and 20%) for soybean meal, with or without phytase supplementation (1,500 FTU/kg) in isoproteic (27% crude protein (CP)) and isoenergetic diets (3,400 kcal/ED/kg of feed) for silver catfish (Rhamdia quelen) juveniles. Methods: A total of 360 fish (weight: 15.77 ± 0.56 g) were randomly distributed in 24 tanks in a completely randomized design following a factorial scheme (3x2) with 4 replicates. The fish were evaluated on the following variables after 90 days: productive performance, hematological variables, histology of intestinal tissue, bromatological composition of carcass, and composition of bone mineral matter. Results: 20% dietary inclusion of sunflower meal improved weight gain and protein efficiency. No difference was observed in the other treatments and no interactions were observed between the other factors. Conclusion: 20% sunflower meal can be included in the feed of silver catfish as a substitute for soybean meal. Phytase inclusion (1,500 FTU/kg) did not improve the nutritional value of the treatments.

Abstract Background Vestibular migraine (VM) has been recognized as a diagnostic entity over the past three decades. It affects up to 1% of the general population and 7% of patients seen in dizziness clinics. It is still underdiagnosed; consequently, it is important to conduct clinical studies that address diagnostic indicators of VM. The aim of this study was to assess auditory brainstem function in women with vestibular migraine using electrophysiological testing, contralateral acoustic reflex and loudness discomfort level. Methods The study group consisted of 29 women with vestibular migraine in the interictal period, and the control group comprised 25 healthy women. Auditory brainstem response, frequency following response, binaural interaction component and assessment of contralateral efferent suppression were performed. The threshold of loudness discomfort and the contralateral acoustic reflex were also investigated. The results were compared between the groups. Results There was a statistically significant difference between the groups in the frequency following response and the loudness discomfort level. Conclusions The current study suggested that temporal auditory processing and loudness discomfort levels are altered in VM patients during the interictal period, indicating that these measures may be useful as diagnostic criteria.

Background: Despite the success of antiretroviral therapy (ART), latent HIV-1 continues to persist in a long-lived population of resting memory CD4+ T cells within those who are infected. Finding a safe and effective means to induce latency reversal (LR) during ART to specifically expose this latent HIV-1 cellular reservoir for immune elimination has been a major barrier to a functional cure. Methods: In this study, we test the use of antigen-presenting type 1-polarized, monocyte-derived dendritic cells (MDC1) generated from chronic HIV-1-infected individuals on ART as a means to induce HIV-1 latency reversal in autologous CD4+ T cells harboring replication-competent provirus. We use the same MDC1 for ex-vivo generation of autologous HIV-1 antigen-specific CD8+ cytotoxic T cells (CTL) and test their effector responses against the MDC1-exposed HIV-1- infected CD4+ T cell targets. Findings: MDC1 presentation of either HIV-1 or cytomegalovirus (CMV) antigens to CD4+ T cells facilitated HIV-1 LR. This antigen-driven MDC1-mediated LR was sharply diminished with blockade of the CD40L/CD40 ‘helper’ signaling pathway. Importantly, these antigen-presenting MDC1 also activated the expansion of CTL capable of killing the exposed HIV-1-infected targets. Interpretation: Inclusion of virus-associated MHC class II ‘helper’ antigens in MDC1-based HIV-1 immunotherapies could serve both as a targeted means to safely unmask antigen-specific CD4+ T cells harboring HIV-1, and to support CTL responses that can effectively target the MDC1-exposed HIV-1 cellular reservoir as a functional cure strategy. Fund: This study was supported by the NIH-NAID grants R21-AI131763, U01-AI35041, UM1-AI126603, and T32-AI065380. Keywords: HIV-1 latency reversal, Dendritic cells, Cytomegalovirus, T cells, CD40 ligand, Immunotherapy